Fused quartz tubing for pharmaceutical packaging

ABSTRACT

A high silica glass composition comprising about 92 to about 99.9999 wt. % SiO 2  and from about 0.0001 to about 8 wt. % of at least one dopant selected from Al 2 O 3 , CeO 2 , TiO 2 , La 2 O 3 , Y 2 O 3 , Nd 2 O 3 , other rare earth oxides, and mixtures of two or more thereof. The glass composition has a working point temperature ranging from 600 to 2,000° C. These compositions exhibit stability similar to pure fused quartz, but have a moderate working temperature to enable cost effective fabrication of pharmaceutical packages. The glass is particularly useful as a packaging material for pharmaceutical applications, such as, for example pre-filled syringes, ampoules and vials.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a Continuation of U.S. application Ser. No.13/477,396, filed May 22, 2012, which is a Continuation-in Part of U.S.application Ser. No. 11/557,805, filed Nov. 8, 2006, which claims thebenefit of U.S. Provisional Application 60/805,300 filed Jun. 20, 2006,each of which is incorporated by reference in its entirety. ThisApplication also claims the benefit of U.S. application Ser. No.13/391,527, filed Feb. 24, 2012, and to PCT ApplicationPCT/US2010/046189, filed Aug. 20, 2010, which claims priority to and thebenefit of U.S. Provisional Patent Application No. 61/235,823, entitled“Fused Quartz Tubing for Pharmaceutical Packaging,” filed on Aug. 21,2009, each of which is incorporated herein in its entirety by reference.

BACKGROUND OF THE INVENTION

In glass applications such as liquid crystal panels, opticalcommunication devices for instance optical filters and optical switches,recording medium, halogen and High Intensity Discharge (HID) lamps etc.the consistency of the glass substrate properties is quite critical.High-energy laser systems employ multiple large pieces of opticalquality glass, sometimes thousands of large size laser glass pieces, andit is imperative for the pieces to have consistent optical quality.Glass compositions, similarly to fused quartz compositions, arecharacterized by a few fundamental properties affecting themanufacturing of or the properties of products employing thecompositions, i.e., viscosity, % transmission, OH level to name a few.The effect of OH (hydroxyl) on viscosity of glass or quartz is widelyknown. FIG. 1, for instance, illustrates the viscosity curves of highpurity quartz made with various OH concentrations. As seen from theFigure, viscosity of glass drastically drops with increased hydroxylconcentration. If glass or quartz has batch-to-batch or within-batchvariations in the OH level, it will result in inconsistentmanufacturability and product quality. From a lamp manufacturer'sperspective, variations in the glass properties impact the yields of thehigh-speed lamp production lines, requiring undesirable and frequentadjustments made to the equipment to account for the variations in theglass properties.

Almost all arc discharge lamps and many high intensity filament lamps,such as tungsten-halogen lamps, emit ultraviolet (UV) radiation whichmay be harmful to human eyes and skin. As disclosed in U.S. Pat. Nos.2,895,839; 3,148,300; 3,848,152; 4,307,315 and 4,361,779, lamps havebeen developed having a light source which emits both UV and visiblelight radiation enclosed within a vitreous envelope of fused quartz.U.S. Pat. Nos. 2,221,709; 5,569,979; 6,677,260 disclose fused quartzcompositions containing UV-absorbing materials, or dopants as they arecalled, in the form of tubings or rods for use in making lamps, e.g., aslamp envelopes with properties to absorb UV radiation.

U.S. Patent Publication No. 20040063564A1 discloses a composition usefulfor forming glass substrates for use in information recording medium,with desirable properties such as specific linear thermal expansioncoefficient, fracture toughness, and a predetermined surface hardness.In applications for making bulk glass articles such as fiberglass, it isalso useful to have consistency in the glass compositions to obtain thedesired ranges of properties such as viscosities, humidity resistance,and the like. U.S. Patent Publication No. 20020077243A1 discloses acomposition for making glass fiber filters for use in micro-electronicclean room environments.

Due to the bulk volume of the feedstock making up the glass composition,there is a wide batch-to-batch variation in glass compositions as wellas in the properties of products made from glass compositions of theprior art. It is important to have consistent properties in a glasscomposition such that products made thereof have properties that areuniform or varying in a narrow range. Additionally, the consistentproperties allowing manufacturers to run production lines with minor orno adjustments in the line, for high productivity and consistently goodglass products. In one aspect, the invention provides a novel glasscomposition and a method for making glass products with uniformproperties, as measured by the standard deviation.

Glasses also find application in pharmaceutical packaging. There hasbeen a recent trend in the pharmaceutical market toward the increaseduse of biological (protein-based) drugs that are more “sensitive” thantraditional drugs. With these types of drugs, the topic ofdrug/container interaction becomes increasingly important due to thelower stability of these drugs and their propensity to degrade duringstorage, especially when formulated as a liquid. Because of this,extractable substances (e.g. dissolved cations) coming from thepharmaceutical packaging container can cause issues with regard toefficacy and purity with these drugs (including drug instability,toxicity, etc). A Review of Glass Types Available for Packaging, S. V.Sangra, Journal of the Parenteral Drug Association, Mar.-pr., 1979, Vol.33, No. 2, pp. 61-67.

Cationic extraction from traditional glasses used in pharmaceuticalpackaging can create issues with the purity and/or effectiveness of suchprotein-based drugs. The mechanism of cationic extraction is typicallyhydronium/alkali ion exchange that causes a pH increase, which is thenfollowed by bulk dissolution, especially in Type I (e.g., borosilicate,such as Schott Fiolax®) and Type II (soda lime silicate) glasses. Thepoor chemical durability of these glasses arises from the fact thatsoluble cations, such as Na⁺, Li⁺, K⁺, Mg²⁺, Ca²⁺ and/or Ba²⁺ are usedto flux these glasses to achieve a suitably low working pointtemperature that makes them highly processable with standard glassmelting equipment (see, e.g., U.S. Pat. Nos. 5,782,815 and 6,027,481).

Glass particle generation due to delamination is one of the majorconcerns in pharmaceutical packaging industries when Type I and Type IIglasses are used as the container for pharmaceutical products.Delamination occurs when top layers of a glass separate at a scale thatis barely visible or invisible to the naked eyes as shown in FIG. 1 ofRonald G Iacocca, “The Cause and Implications of Glass Delamination”,Pharmaceutical Technology, 2011, pp s6-s9, the disclosure of which isincorporated herein by reference in its entirety. The particles becomesuspended in drug solutions, posing a serious risk to the consumer.

Glasses without chemical modifiers (e.g., alkali metals, borates,alkaline earth metals) such as fused quartz glass are preferable from achemical purity (low extractables) and chemical durability perspective,but such glasses may be difficult to manufacture due to the highprocessing temperatures required (typically >2,000° C.). Even when fusedquartz glasses can be melted and formed into tubing, it is then oftendifficult to flame convert them into pharmaceutical packages (vials,syringe barrels, ampoules, etc), due to a high working point temperature(>1,700° C.). Thus, such glasses have generally not been used tomanufacture pharmaceutical packaging. U.S. Pat. Nos. 6,200,658 and6,537,626 show that efforts have been made to coat the interior surfacesof traditional glass containers with a layer of silica to reduceextractables (e.g., Schott Type I Plus®) and glass particles that areproduced through delamination. Providing coated articles, however, arecumbersome and expensive and, therefore, not widely accepted in thepharmaceutical packaging market. Thus, there is a need for acost-effective pharmaceutical packaging glass that exhibits lowextractables and leaching with a moderate working point temperature thatcan be used in pharmaceutical packaging applications.

BRIEF DESCRIPTION

Drugs are packaged in various glass pharmaceutical containers, includingsingle-use pre-filled syringes, cartridges, ampoules, vials and thelike. In one aspect, the present invention provides a pharmaceuticalpackaging comprising a low softening point high silicate (substantiallymodifier free) glass tubing that can be flame converted to formtraditional pharmaceutical packages (e.g., syringe barrels, cartridges,ampoules, vials, etc). The tubing does not contain appreciable amountsof traditional glass modifiers (e.g., alkali metals, alkaline earthmetals, and borate ions), and the resulting packaging is thus highlyresistive to cationic extraction when placed in contact with anaqueous-based solution intended for drug formulation. In one embodiment,the inventions provide a pharmaceutical packaging that exhibits littleor no glass particle generation through delamination. Applicants havefound that the working point temperature and the viscosity of the glass(at a particular temperature) can be reduced through additions ofnon-traditional-modifiers to achieve a working point temperature that isacceptable for use in the fabrication of pharmaceutical packaging usingthermal process (e.g., flame conversion).

In one aspect, the invention provides a glass composition comprising alot of glass articles, the glass composition containing 40 to 99 wt. %SiO₂, wherein the glass composition has a softening temperature rangingfrom 500° C. to 1700° C., and wherein the standard deviation ofsoftening temperature measurements obtained from 10 or more randomlyselected samples of glass articles produced from the lot is 10° C. orless.

In another aspect, the invention provides a process for making a glassproduct comprising the steps of: (a) forming a first blend of 0.02 to0.50 wt. % of a dispersant with 1 to 25 wt. % of a dopant selected fromthe metal oxide group of Al₂O₃, TiO₂, CeO₂, Nd₂O₃, TiO2, BaO, SrO, MgO,Sb₂O₃, Y₂O₃, Co₃O₄, Cu₂O, Cr₂O₃ and mixtures thereof, wherein thedispersant is a fumed metal oxide having a BET of 50-400 m²/g and a meanparticle size of <1 μm; (b) blending the first blend into 92-99 wt. %SiO₂ forming a quartz mixture; (c) producing a melt of molten glass fromthe mixture; and (d) passing the molten glass along a tool to form aglass product. In one embodiment, the glass product is in the form of atubing, a rod, or a blank. In a another embodiment, the fumed metaloxide is selected from at least one of silica or a metal oxide alreadypresent in the dopant.

The invention further relates to a glass product, comprising 92-99 wt. %of SiO₂, 1 to 8 wt. % of a dopant selected from the metal oxide group ofAl₂O₃, CeO₂, TiO₂, Nd₂O₃, TiO2, B₂O₃, BaO, SrO, MgO, Sb₂O₃, Y₂O₃, Co₄O₄,Cu₂O, Cr₂O, and mixtures thereof; and 0.02 to 0.50 wt. % of a fumedmetal oxide having a BET of 50-400 m²/g and a mean particle size of <1μm, and wherein the fumed metal oxide is SiO₂ or a metal oxide presentin the dopant, wherein the viscosity of a plurality of products preparedfrom the same batch exhibits a standard deviation of less than 10 degreeCelsius.

In one aspect, a glass composition in accordance with the presentinvention utilizes non-traditional modifier dopants (oftentimes referredto as intermediates within the glass science community), such as Al₂O₃,G_(e)O₂, Ga₂O₃, CeO₂, ZrO₂, TiO₂, Y₂O₃, La₂O₃. Nd₂O₃, other rare earthoxides, and mixtures of two or more thereof, to achieve a high wt %content silica glass with lower working point temperature, and lowerviscosity (at a particular temperature) as compared to pure fused quartzwhile retaining the chemical inertness with respect to drugs similar topure fused quartz glass. It has been found that incorporatingnon-traditional modifiers into the fused quartz glass effectivelyreduces the working point temperature by up to several hundred Kelvinand, therefore, enables rapid flame conversion/processing of tubing intopharmaceutical containers, while also enabling the glass to retain theexcellent chemical durability and a resistance to cationextraction/leaching characteristic of quartz glass.

The dopants listed above are selected based on the ability of thesecations to reduce the working temperature of fused silica, whileretaining a chemical durability that will be extremely resistant tocationic extraction when the resulting glass is placed into contact withan aqueous solution intended for drug formulation. This resulting,modified glass tubing can be fabricated into various pharmaceuticalpackages, including syringe barrels, cartridges, ampoules, and vials. Atthe same time, the chemical inertness of this glass renders it superiorto borosilicate and soda lime silicate glasses that are traditionallyused for pharmaceutical packaging.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph illustrating the change in the viscosity of highpurity quartz glass as a function of OH concentrations.

FIG. 2 is a photograph comparing lamp envelopes made from the glassproducts of composition in one embodiment of the invention, i.e., 2 wirelamps on the right vs. 2 lamp envelopes made from a glass productcomposition in the prior art (lamps on the left).

FIG. 3 is a graph comparing the variations in UV transmission data forsamples from the glass products of the invention as made from the samebatchlot vs. samples from glass products made from a composition in theprior art.

FIG. 4 is a graph comparing the variations in UV transmission data overa range of 200-800 nm, for samples from the glass products of theinvention as made from the same batchlot vs. samples from commerciallyavailable glass products in the prior art.

FIG. 5 is a graph comparing the average OH concentration and standarddeviation of an embodiment of the glass composition of the invention vs.reference samples from commercially available glass products in theprior art.

FIG. 6 is a photograph comparing a glass “puck” made from the glassproducts of composition in one embodiment of the invention vs. a glasspuck made from a glass product composition in the prior art,particularly with respect to degree of clarity (or transmission throughthe glass).

FIG. 7 illustrates the viscosity as a function of temperature of glasscompositions in accordance with aspects of the present invention.

DETAILED DESCRIPTION

As used herein, approximating language may be applied to modify anyquantitative representation that may vary without resulting in a changein the basic function to which it is related. Accordingly, a valuemodified by a term or terms, such as “about” and “substantially,” maynot to be limited to the precise value specified, in some cases.

As used herein, the term “functionalized” may be used interchangeablywith “surface functionalized,” “functionalized surface,” “coated,”“surface treated,” or “treated,” referring to the coating of the silicaand dopant components with the dispersing agent of the invention. Asused herein, “coating agent” is used interchangeably with “dispersing”agent.

Although the terms may be used to denote compositions or articles ofdifferent materials (different silica concentrations), as used herein,the term “glass” may be used interchangeably with “quartz glass” or“quartz” or “fused quartz,” referring to a composition, a part, aproduct, or an article formed by melting a mixture comprising natural orsynthetic sand (silica). It is well known that the viscosity of a glasswill decrease as its temperature increases. Thus, as used herein, theterms “working point temperature” and “working temperature” are bothused to mean the temperature at which the glass reaches a viscosity of10⁴ poise or below, and the softening point describes the temperaturewhere the viscosity reaches 10^(7.6) poise. Either or both natural orsynthetic sand (silica) can be used in the composition of the invention,and the term silica is used to denote compositions comprising eithernaturally occurring crystalline silica such as sand/rock, syntheticallyderived silicon dioxide (silica), or a mixture of both. The term “sand”may be used interchangeably with silica, denoting either natural sand orsynthetic sand, or a mixture of both.

As used herein, the term “lot” when applied to a batch process formaking the glass products of the invention, refers to glass articlesmade from a single batch of sand feed of at least 100 kg in totalcomposition of sand and other additives. When applied to a continuousprocess of making glass products, the term lot refers to the glassarticles having a total weight of at least 100 kg, as continuouslyproduced from a process.

In one embodiment, the invention provides a glass composition withminimum variations in the properties of articles formed from the samebatchlot of the composition, e.g., fiberglass, tubings, rods, blanks,plates, etc., via the use of at least a dispersing/coating agent thathelps the dopant(s) adhere to the sand grains. The dispersant maximizesthe composition homogeneity within the same batchlot, such that thearticles or parts manufactured from the same batchlot have minimumvariations in properties such as viscosity, OH—, and the like. Thearticles made from the composition of the invention with minimumvariations in properties can be subsequently melted, drawn, formed ortailored into a final glass product.

Sand Component: The silica (SiO₂) used in the glass compositions of thepresent embodiments can be synthetic sand, natural sand, or a mixturethereof. In one embodiment, the amount of SiO₂ in the glass compositionranges from about 82 to about 99.9999%. In another embodiment, theamount of SiO₂ in the glass composition ranges from about 92 to about99.9999%; from about 96 to about 99.9999 wt. %; from about 97 to about99.9999 wt. %; even from about 98 to about 99 wt. %. In anotherembodiment, the glass comprises a light-transmissive, vitreouscomposition with an SiO₂ content of at least about 90 wt. %. In stillanother embodiment of a quartz composition with a high melting point, atleast 95 wt. % SiO₂ is used. In yet another embodiment, the glasscomposition has a SiO₂ concentration of at least about 97 wt. %; atleast about 98 wt. %; even at least about 99 wt. %. Here as elsewhere inthe specification and claims, ranges can be combined to form new andnon-disclosed ranges.

Dispersing Agent Component. In one embodiment, the agent is a fumedmetal oxide selected from alumina, silica, titania, ceria, neodymiumoxide, and mixtures thereof, having a BET value of 50 m²/g to 1000 m²/gand a particle size of less than 25 microns. Fumed metal oxides areproduced using processes known in the art, in one example, thehydrolysis of suitable feed stock vapor (such as silicon tetrachloridefor fumed silica) in a flame of hydrogen and oxygen.

The surface area of the metal oxides may be measured by the nitrogenadsorption method of S. Brunauer, P. H. Emmet, and I. Teller, J. Am.Chemical Society, Volume 60, Page 309 (1938) and is commonly referred toas BET. In one embodiment, the dispersing agent has a BET of 100 m²/g toabout 400 m²/g. In another embodiment, the fumed metal oxide dispersingagent has a mean particle size of 15 μm or less. In another embodiment,the fumed metal oxide has a mean particle size of less than 1.0 μm. Inanother embodiment, the fumed metal oxide has a mean particle size of0.1-0.5 μm with a BET value of 50 m²/g to 100 m²/g.

The dispersing agent is added to the glass composition in an amountranging from 0.02 to 0.50 wt. % (based on the total weight of the finalglass composition). In one embodiment, dispersant is added to the sandmixture in an amount ranging from 0.04 to 0.30 wt. %. In anotherembodiment, from 0.05 to 0.15 wt. %. In still another embodiment, from0.05 to 0.10 wt. %.

In one embodiment, it is added directly to the glass composition alongwith the dopants. In another embodiment, it is pre-mixed with at leastone of the dopant(s) or a portion of the dopant(s), forming a masterbatch, which is subsequently added to the sand mixture. In anotherembodiment, the dispersant is mixed with part or all of the selecteddopant(s)s forming a master batch, which master batch is subsequentlyadded to the sand mixture and other dopants. In another embodiment, thedispersant is mixed with all or some of selected dopants as well as someof the sand to form a master batch, which master batch is subsequentlyadded to the final sand mixture. In yet another embodiment, thedispersant is mixed with all of selected dopants as well as sand forminga master batch, which master batch is subsequently added to the sandmixture.

In one embodiment, the dispersing agent is untreated fumed silica. Inanother embodiment wherein Al₂O₃ is used as a dopant, the dispersingagent is fumed alumina. In another embodiment wherein CeO₂ is added as adopant, fumed ceria is used as a dispersing agent. In another embodimentwherein one of the dopants used is Nd₂O₃, a mixture of fumed neodymiumoxide and fumed silica is used as the dispersing agent. In yet anotherembodiment and regardless of the dopant(s) used, the dispersant isselected from fumed metal oxides with little adverse impact to theproperties of the glass products, i.e., the group consisting of fumedalumina, silica, titania, ceria, neodymium oxide, and mixtures thereof.

Dopant Component(s): Depending on the desired properties in the finalproduct, a number of different dopants and mixtures thereof may be addedto the silica. Dopants are selected such that they reduce the workingpoint temperature of the glass and its viscosity at a particulartemperature and also such that the final glass product will exhibit lowextractables and/or leaching of ions into drugs, aqueous drugformulations, or other compositions that come into contact therewith.Particularly suitable dopants are those that exhibit low solubility inthe various (aqueous-based) contemplated drug compositions. Examples ofsuitable dopants include Al₂O₃, G_(e)O₂, Ga₂O₃, CeO₂, ZrO₂, TiO₂, Y₂O₃,La₂O₃, Nd₂O₃, other rare earth oxides, and mixtures of two or morethereof. In one embodiment, the dopant is neodymium oxide Nd₂O₃. Inanother embodiment, the dopant is aluminum oxide by itself, e.g., Al₂O₃,or a mixture of aluminum oxide and other dopants. In another embodiment,the dopant is CeO₂. In yet another embodiment, titanium oxide (TiO₂) maybe added. In another embodiment, the dopant comprises europium oxide,Eu₂O₃, by itself, or in combination with other dopants such as TiO₂ andCeO₂. In still another embodiment, the dopant is yttrium oxide. Ofcourse, as previously described, the glass composition may comprise asingle dopant or any suitable combination of two or more differentdopants.

In one embodiment, the dopant is present in an amount of from about0.0001 to about 8% by weight of the total composition. In anotherembodiment, the dopant(s) may be present in an amount of from about 0.01to about 8 wt. %, and in still another embodiment from about 0.1 toabout 8 wt. %. In another embodiment, the dopant is present in an amountof from about 0.5 to about 5% by weight of the glass composition. Itwill be appreciated that some dopants may be added in an amount as lowas about 0.01 wt. %, and may be, for example, in a range of from about0.01 to about 0.1 wt. % including, for example, from about 0.01 to about0.05 wt. %. In one embodiment, the dopants are to be added in an amountto reduce the working point temperature of the resultant quartzcomposition to less than 1,650° C. In another embodiment, the totalamount of dopants is in the range of about 0.01 to about 8 wt. %. Instill another embodiment, the total amount of dopant ranges from about0.1 to about 8 wt. %.

The glass compositions, in one embodiment, contain a low concentrationof metal impurities. The impurities may comprise metals other than thedopant metals. In one embodiment, the metal impurities include metalsother than Al, Ge, Ga, Ce, Zr, Ti, Y, La, Nd, or other rare earthmetals. In one embodiment, the total concentration of metal impuritiesis less than 1.0 wt. % or less. In another embodiment, the totalconcentration of metal impurities is less than 0.5 wt. % or less. Instill another embodiment, the total concentration of metal impurities isless than 0.015 wt. % or less. In one embodiment, the metal impuritiesinclude alkali metals. In one embodiment, the total alkali metalconcentration is less than 1.0 wt. % or less. In another embodiment, thetotal alkali metal concentration is less than 0.5 wt. % or less. Instill another embodiment, the total alkali metal concentration is lessthan 0.015 wt. % or less. In one embodiment, the glass compositioncomprises about 3 wt. % or less of B₂O₃; about 2 wt. % or less of B₂O₃;about 1 wt. % or less of B₂O₃; even about 0.1 wt. % or less of B₂O₃.

In one embodiment, the dopant is CeO₂ in an amount of 0.1-5% by weight.Cerium is the only rare-earth element that absorbs UV radiation whileexhibiting no absorption in the visible region of the spectrum. Inanother embodiment, titanium or titanium oxide may be added, wherein theaddition of titanium sometimes produces yellowish-brown glass. Inanother embodiment, the dopant comprises europium oxide Eu₂O₃ by itself,or in combination with other dopants such as TiO₂ and CeO₂. In a furtherembodiment, dopants such as CaO and/or magnesium oxide MgO may be addedto give stability to the composition.

In one embodiment of a glass composition containing 95-99.9 wt. % SiO₂and excluding the dispersing agent(s), dopants are added in an amountfor a composition of 95-99.9 wt. % SiO₂, ranging from 0.1 to 5 wt. %Al₂O₃, and other impurities in an amount not exceeding 150 ppm (total).In another embodiment, the composition comprises 95-99.9 wt. % SiO₂, 0.1to 5 wt. % Al₂O₃ as a dopant, 0.1 to 400 ppm titanium (element), 0.1 to4000 ppm Cerium (in elemental form or CeO₂), and other impurities notexceeding 150 ppm (total). In still another embodiment, the compositioncomprises 95 to 99.9 wt. % SiO₂, 0.1 to 5 wt. % Al₂O₃ as a dopant, 0.1to 400 ppm Titanium (element), 0.1 to 4000 ppm Cerium (in elemental formor CeO₂), 0.01 to 2 wt. % Nd₂O₃, and other impurities not exceeding 150ppm (total).

In one embodiment for a glass composition for the absorption of redlight in the range of 560-620 nm, and excluding the amount of dispersantadded, added dispersant, the composition comprises 95-110 parts byweight SiO₂, 0.5 to 1.2 parts by weight CeO₂, 0.5 to 2.5 parts be weightof Nd₂O₃, 0.1 to 1 parts by weight of Al₂O₃, optionally 0.001 to 0.1parts by weight of Eu₂O₃, 0.001 to 0.1 parts by weight of TiO₂, 0.001 to0.5 parts by weight of BaO.

Depending on the identity of the dopant and the amount of dopant presentin the glass composition, the subsequent doped fused quartz glasscomposition exhibits a working point in the range of from about 1000 to2,000° C. In one embodiment, the glass composition exhibits a workingpoint of from about 1400 to about 1,900° C. In another embodiment, thedoped fused quartz glass has a working point of about 1,700° C. or less,which may be much lower than the working point of undoped quartz glass.The glass compositions may have a softening point of from about 500 toabout 1,700° C. In one embodiment, the glass composition has a softeningpoint of from about 1,000 to about 1,600° C. In another embodiment, theglass composition has a softening point of from about 1,400° C. to about1,600° C. Due to these lower working points exhibited by these dopedglasses, the rods or tubes may be subsequently shaped into variouspharmaceutical packaging articles more easily (by means of for instanceflame conversion) than would an undoped quartz glass.

In another embodiment, UV absorbers or blockers may be added to theglass composition to minimize the transmission of UV radiation to thecontents of the pharmaceutical package, thus protecting the drugcontents held within from degradation. Suitable UV absorbers include Ti,Ce, and Fe. Concentrations of 2000 ppm and less are preferably used withconcentrations of Fe down to <100 ppm to reduce coloration but stilleffectively block UV. Other transition metals that have similar impactand may be used at low levels without impacting color too much for thinwall vessels are Cr, Mn, Mo, V, and Zn. Oxidation state should becontrolled (usually to the highest oxidation state) to minimizecoloration.

In an alternate embodiment, undoped silica is used to make the glass andsubsequent pharmaceutical packaging articles. Although having a higherworking point temperature, these articles will also have the desired lowamount of extractables as the doped glass composition above.

A glass composition in accordance with the present invention can be usedto form a homogenous, fused glass article. A glass article formed from aglass composition in accordance with the present invention may exhibitleaching characteristics superior to borosilicate (BSi) glasses and/orsoda lime (Na—Ca) glasses. In one embodiment, a glass article inaccordance with the present invention exhibits superior leachingcharacteristics with respect to cations or metals when the glass issubjected to HCl digestion. As used herein, “HCl digestion” meanshydrothermally treating a 10.0 g sample of a glass article (that hasbeen crushed into 5-10 nm in size) with 50 ml of 0.4 M HCl solution in aParr teflon digestion bomb at 121° C. for 2 hours. In one embodiment,the leaching characteristics of the glass may be represented in terms ofextractable metal concentration, which refers to the concentration ofmetal extracted from the glass article when subjected to HCl digestion.In one embodiment, a glass article formed from a glass composition has atotal extractable metal concentration of about 8 mg/L or less whensubjected to HCl digestion, the total extractable metal concentrationbeing represented by the total concentration of Al, B, Na, Ca, K, Li,Ba, and Mg extracted upon HCl digestion. In another embodiment, a glassarticle formed from a glass composition has a total extractable metalconcentration of about 5 mg/L or less when subjected to HCl digestion,the total extractable metal concentration being represented by the totalconcentration of Al, B, Na, Ca, K, Li, Ba, and Mg extracted upon HCldigestion. In still another embodiment, a glass article formed from aglass composition has a total extractable metal concentration of about 1mg/L or less when subjected to HCl digestion, the total extractablemetal concentration being represented by the total concentration of Al,B, Na, Ca, K, Li, Ba, and Mg extracted upon HCl digestion.

In one embodiment, the total extractable metal concentration is fromabout 0.01 to about 8 mg/L; from about 0.05 to about 5 mg/L; even fromabout 0.1 to about 1 mg/L. Here as elsewhere in the specification andclaims, numerical values can be combined to form new or undisclosedranges.

In one embodiment, a fused glass article formed from the glasscomposition exhibits the following leaching characteristics whensubjected to HCl digestion: Na (<0.1 mg/L), Ca (<0.05 mg/L), B (<0.01mg/L), Al (<0.05 mg/L), Mg (<0.01 mg/L), or K (<0.01 mg/L). In oneembodiment, a fused glass article formed from the glass compositionexhibits the following leaching characteristics when subjected to HCldigestion: Na (<0.1 mg/L), Ca (<0.05 mg/L), B (<0.01 mg/L), Al (<0.05mg/L), Mg (<0.01 mg/L), and K (<0.01 mg/L). In one embodiment, a glassarticle has the following leaching characteristics when subjected to HCldigestion: Na (<7.0 mg/L), Ca (<1.0 mg/L), B (<2.5 mg/L), Al (<1.25mg/L) Ba (<0.003 mg/L), Fe (<0.01 mg/L), K (<0.03 mg/L), Mg (<0.01mg/L), As (<0.02 mg/L), Cd (<0.001 mg/L), Cr (<0.008 mg/L), Pb (<0.009mg/L), and Sb (<0.01 mg/L). In another embodiment, a glass article hasthe following leaching characteristics: Na (<0.1 mg/L), Ca (<0.05 mg/L),B (<0.01 mg/L), Al (<0.05 mg/L), Fe (<0.05 mg/L) Mg (<0.01 mg/L), K(<0.01 mg/L), As (<0.02 mg/L), Cd (<0.001 mg/L), Cr (<0.008 mg/L), Pb(<0.009 mg/L), and Sb (<0.01 mg/L).

Process for Making Glass Compositions/Products:

Glass compositions can be formed in one embodiment, using a dispensingagent as described herein. The use of dispersants in the composition ofthe invention facilitates the blending of the dopants in the sand feed,and thus the homogeneity of glass products made. The composition can bemade by via a batch method (one-at-a-time melting process) or acontinuous melting method.

In one embodiment of a batch process, the glass products are made frombatches of sand feed in the form of barrels or bags of sand, with eachbarrel or bag having a weight of at least 100 lbs. In anotherembodiment, glass products are made from batches of at least 100 kg ofsand feed for each batch, with the sand being supplied in barrels ofsizes of 100 kg. In yet another embodiment, the sand is supplied inbatches of 300 lbs. for each bag or barrel, thus making glass articlesout of single batches of at least 300 lbs. each.

In one embodiment, the dispersing agent, i.e., the fumed metal oxide(s)such as fumed silica, fumed alumina, etc., is first mixed with 20-100%of a single dopant, a few dopants, or all of the dopant(s), forming amaster batch or concentrate. The fumed metal oxide dispersing agent canbe the same or different metal oxide(s) as the dopant material(s). Themixing/blending may be conducted in a processing equipment known in theart, e.g., blenders, high intensity mixers, etc, for a sufficient amountof time for the dopants to be thoroughly coated with the dispersingagent. In one embodiment, a mixture of fumed silica as the dispersingagent is mixed with dopants such as Al₂O₃, CeO₂, Nd₂O₃, etc., in aTurbula® mixer between 1 to 5 hours forming a master batch. Though notbound by theory, it is believed that the fumed silica acts as a sandgrain “coating” agent and attracts smaller particles of dopant such asaluminum oxide, thus providing a more uniform mix.

In the next step, the master batch containing the coated dopant(s) isadded to the natural/synthetic sand feed and the remainder of theuncoated dopants, if any, and mixed thoroughly in an equipment such as atumbler, a sand muller, etc.

In one embodiment of the invention, the homogenous mix is calcined orheated at a temperature between 500-1500° C. for a sufficient period oftime, e.g., for 0.5-4 hrs, to dry out the sand. The mixture issubsequently fused at a sufficiently high temperature to form glassproducts. The temperature depends on the glass composition, and inquartz compositions (having >95% SiO₂), the mixture is fused at atemperature of >2000° C. and ranging to 2500° C., giving a vitreousmaterial. In one embodiment, the mixture is continuously fed into a hightemperature induction (electrical) furnace operating at temperatures inthe range of 1400-2300° C., forming tubes and rods of various sizes. Inanother embodiment, the mixture is fed into a mold wherein flame fusionis used to melt the composition, and wherein the molten mixture isdirected to a mold forming the glass particle.

In one embodiment wherein the glass product is in the form of continuoustube drawing, e.g., the tubings can be made by any process known in theart including the Danner process, the Vello process, a continuous drawprocess or modified processes thereof.

In one embodiment, a glass composition is formed by mixing a high puritysilicon dioxide (natural or synthetic sand) with at least one dopantselected from Al₂O₃, G_(e)O₂, Ga₂O₃, CeO₂, ZrO₂, TiO₂, Y₂O₃, La₂O₃,Nd₂O₃, other appropriate rare earth oxides, and mixtures of two or morethereof. The dopant(s) may be first mixed with up to 5 wt. % SiO₂ fumedsilica before they are mixed into the final SiO₂ batch prior to glassmelting. The mixing/blending may be conducted in processing equipmentknown in the art, e.g., blenders, high intensity mixers, etc, for asufficient amount of time for the dopants to be thoroughly mixed withthe silica-rich batch. This batched composition may be dried and thenfused at 1,800° C. to 2,500° C. in a high induction furnace or flamefused into a homogeneous glass. In one embodiment, the mixture iscontinuously fed into a high temperature induction (electrical) furnaceoperating at temperatures in the range of up to about 2,500° C., formingtubes and rods of various sizes. In another embodiment, the mixture isfed into a mold wherein flame fusion is used to melt the composition,and wherein the molten mixture is directed to a mold forming the glassarticle.

Glass Products from Composition of the Invention.

Although not bound by theory, it is believed that the dispersing agentin the form of fumed metal oxide with large surface areas functions as amixing agent, helping the dopants stick or adhere to the sand grains,thus allowing a homogeneous mix and subsequently, glass products havingvery little variations in properties for products resulting from thesame batch of sand. The glass products can be of an intermediate form ofglass tubing, for use in manufacturing halogen lamb bulbs or watertreatment lamps; solid glass rods or performs for making lamp envelopes;blanks, glass plates or sheets for automotive glazing. The glassproducts can be of a final bulk form such as glass fiber.

In one embodiment, the tubings have sizes ranging from 1 to 500 mmoutside diameter (OD), with a thickness ranging from 1 to 20 mmdepending on the size of the tubing. The length of the tubings rangesfrom 24 to 60″ for tubings with O.D of less than 100 mm and 24 to 96″for tubings with OD of greater than 100 mm.

In another embodiment of making glass preforms or rods using processesknown in the art, including a continuous draw process of at least twosteps. In the first step, an elongated, consolidated preform having anaperture is drawn to a reduced diameter preform. The second stepinvolves drawing the reduced diameter preform into a rod at a lowertemperature than the first step to reduce the formation of inclusions inthe glass rod during drawing. In one example, the rods have OD rangesfrom 0.5 mm to 50 mm. In one embodiment, the rods are made in a drawprocess

In one embodiment of a continuous process, e.g., making glass plates foruse in automotive applications, after the raw materials are admixed andmelted, the melt is feed to a conventional float glass furnace andsubsequently into a molding forming the final product.

Uniform Properties of Glass Products:

In one embodiment, the glass products of the invention are characterizedas having uniform properties for glass articles produced from the samelot, i.e., articles or pieces produced from the same mixing batch witheach batch employing a minimum size of at least 100 kg. of sand, orglass articles continuously produced from a continuous process with atotal weight of at least 100 kg.

Uniform properties means little variations in the properties of theglass pieces or products from the same lot are measured. The propertiesrange from chemical properties such as OH level to physical propertiessuch as viscosity, softening point, annealing point, etc.; thermalproperties such as coefficient of thermal expansion; mechanicalproperties such as compressive strength; optical properties such astransmission and color, etc. As used herein a plurality of productsmeans at least 10 samples, randomly selected from products/pieces madefrom the same lot.

Melting temperature, softening temperature, strain temperature, andannealing temperature respectively vary according to the glasscomposition, i.e., ranging from as low as 600° C. as softening point forlead borate glass to 1650° C. for fused silica. The glass articles ofthe invention have different working temperatures depending on theamount of silica present in the composition. However, they are allcharacterized as varying little in the melting temperature, softeningtemperature, strain temperature, and annealing temperature for glassarticles made from the same lot. In one embodiment, the glass articlesmade from the same lot have a standard deviation σ of less than 10° C.in their softening point, bending point, and annealing pointrespectively, as measured from 10 or more randomly selected samples ofglass articles produced from the same lot. In a second embodiment, thestandard deviation is less than 5° C. variation in the melting,softening, bending, and annealing temperatures respectively, frommeasuring at least 10 randomly selected samples.

In one embodiment, glass articles made from the same lot have an averageannealing temperature in the range of 1000-1250° C. (corresponding to alog viscosity of 13.18 Poise), with a standard deviation σ of less than10° C. In a second embodiment, the glass articles have a standarddeviation σ of less than 5° C. for articles made from the same lot.

In one embodiment, the glass articles produced from the same lot have astandard deviation σ of 10 ppm in terms of the average OH concentration.In one embodiment, the glass articles have an average OH concentrationof less than 100 ppm, with a standard deviation σ of less than 10 ppm.In another embodiment, the glass has an average OH concentration of <50ppm, with σ value of less than 5 ppm for glass articles from the samebatch. In yet another embodiment, glass articles from the same lot havean average OH concentration of <30 ppm, with σ value of less than 5 ppm.In a fourth embodiment, glass articles from the same lot have an averageOH concentration of <20 ppm, with σ value of less than 3 ppm.

Glass articles made from the compositions of the invention are alsocharacterized as having excellent dimensional control/stability, e.g.,with little variations in the dimensions of the finished articles madefrom the same mold and out of the same lot. Generally, the dimensionalaccuracy (moldability) of a glass product can be accurately judged byprocess capability (Cpk). Here, “process capability” indicates thedegree of quality that is achieved when the process is standardized, andcauses for abnormality are removed, whereby the process is kept in astable condition. In one embodiment, dimensions of glass articles aremeasured using a micrometer and calipers for at least three dimensions,length, thickness, and width for glass articles in the form of a plate.In a second embodiment, dimensions along the line of length, thickness(of a tubing) and diameter are measured. In one embodiment, the glassarticles of the invention are characterized as having a CpK (processcapability index) of >1.50 in all three quantified dimensions. In asecond embodiment, the glass articles have a CpK of >1.33 for articlesmade from the same lot. In yet another embodiment, the glass articlesare measured in terms of their outer diameter, wall thickness, andovality (variation in the outer diameter around the circumference), andwherein the articles have a CpK of >1.33 for articles from the same lot.

In one embodiment the glass articles as produced from the same lot ofthe invention have an average coefficient of thermal expansion from 25°C. to 320° C. of 0.54*10⁻⁶/K to 5.5*10⁻⁷/K with a standard deviation σof <0.5*10⁻⁷/K. In one embodiment, the glass articles have an averagecoefficient of thermal expansion from 25° C. to 320° C. of less than7.0*10⁻⁷/K, with a standard deviation σ of <7*10⁻⁸/K.

In one embodiment, the glass articles made from the same lot of thepresent invention have a refractive index ranging from 1.40 to 1.68,with a standard deviation for glass articles made from the same lot ofless than 0.001. In one embodiment, the glass articles have a refractiveindex ranging from 1.450 to 1.480 with a standard deviation of less than0.0001 for glass articles made from the same lot.

In one embodiment, the glass articles of the invention comprising95-99.995 wt. % of high purity silicon dioxide display a visibletransmission of above 90% in 400-800 nm wavelength range, with astandard deviation of less than 2% for glass articles produced from thesame lot. In a second embodiment, the glass articles display a visibletransmission of above 90% in 400-800 nm wavelength range and a standarddeviation of less than 0.5% for glass articles produced from the samelot.

Applications and Articles Employing Glass Products:

In one embodiment, the molten glass composition is molded/formed into afinal product such as glass plates or containers. In another embodimentfor use in lamp products, e.g., lamp envelopes of tungsten-halogen lampsystems or lamp sleeves for tungsten-halogen lamps and other hightemperature lighting devices (“high intensity discharge lamps”), themolten glass composition is made into intermediate glass products suchas rods or tubings prior to being formed into the final glassapplication as lamp envelopes or sleeves.

In one embodiment, the composition is used in applications where highcontrast and enhanced visible properties of transmitted or reflectedvisible light can be a benefit. Such uses include, for example,opthalmic glass for eyewear, such as sunglasses, or as glass hosts forlasers. In yet another embodiment, the glass can be made into computerscreens with enhanced contrast properties can lessen visual discomfort,or rear-view mirrors to reduce glare. The glass products with uniformproperties of the invention can also be used in applications such ascontainers for medical, chemical, and pharmaceutical products such asampoules, bottles, reagent containers, test tubes, titration cylindersand the like. In another embodiment, the product is used in applicationssuch as automotive glazing. The glass composition can also be used inbulk glass products such as fiberglass.

In one aspect, glass compositions in accordance with the presentinvention are particularly suitable for forming a pharmaceuticalpackaging article such as, for example, pre-filled syringes, syringebarrels, ampoules, vials, and the like. A pharmaceutical package orarticle formed from the glass compositions should exhibit betterleaching characteristics, i.e., lower leaching of metals, when an innersurface of the package or article is in contact with an aqueouspharmaceutical composition including, but not limited to, drug andmedicinal formulations. In one embodiment, a pharmaceutical packagingarticle comprising the doped glass may be provided such that the articleis substantially free of a coating layer disposed on the surface of thearticle in contact with a pharmaceutical composition. Articles employinga doped glass in accordance with the present invention, may be free of acoating and exhibit leaching characteristics when in contact with apharmaceutical composition that is at least comparable to coated BSi orsoda lime glasses and superior to uncoated BSi or soda lime glasses.

In one embodiment, a pharmaceutical packaging article comprising theglass composition is formed by thermal processing, such as flame fusionconversion process. The article exhibits little or no alkali oxide,alkaline earth oxide, or borate formation at or near the surface of thearticle during the thermal processing. In one embodiment, theconcentration of alkali metals, alkaline earth metals, and/or boron isabout 5 wt % or less within a distance of 5 μm of the surface of thearticle. In one embodiment the concentration of alkali metals, alkalineearth metals, or boron is 1 wt % or less within 5 μm of the surface ofthe article. In one embodiment the concentration of alkali metals,alkaline earth metals, or boron is 100 ppm or less within 5 μm of thesurface of the article. In one embodiment the concentration of alkalimetals, alkaline earth metals, or boron concentration is 10 ppm or lesswithin 5 μm of the surface of the article. The alkali, alkaline earth,or boron concentration within 5 μm of the surface of the article may bedetermined by any suitable method including surface etching followed byInductively Coupled Plasma Mass Spectrometry (ICP-MS). It will beappreciated that the alkali metal or alkaline metal can be derived fromany alkali metal compound or alkaline metal compound including, but notlimited to, oxides or hydroxides of alkali or alkaline metals.

In one embodiment, the pharmaceutical packaging article comprising theglass composition produces 1000 particles/cm² or less when in contactwith a pharmaceutical aqueous solution at pH from about 3 to 10 for 60days. In one embodiment, the article produces 500 particles/cm² or lesswhen in contact with a pharmaceutical aqueous solution at pH from about3 to 10 for 60 days. In one embodiment, the article produces 100particles/cm² or less when in contact with a pharmaceutical aqueoussolution at pH from about 3 to 10 for 60 days. In one embodiment, thearticle produces 50 particles/cm² or less when in contact with apharmaceutical aqueous solution at pH from about 3 to 10 for 60 days. Inone embodiment, the article produces 10 particles/cm² or less when incontact with a pharmaceutical aqueous solution at pH from about 3 to 10for 60 days. The number of particles formed from the glass article maybe determined by any suitable method including a laser particle countinginstrument.

Aspects of the present invention may be further understood with respectto the following examples.

EXAMPLES

In the examples, fumed silica is commercially available fromMatteson-Ridolfi Inc. as Cab-O-Sil M5, with a B.E.T. surface area of 200m²/g and average particle (aggregate) size of 0.2-0.3 μm. The sand usedis a natural sand having a purity level of at least 99.99%, which iscommercially available from a number of sources.

Example 1

A glass composition is made with 96 wt. % high purity silicon dioxide, 4wt. % Al₂O₃ as a dopant, and with other impurities kept at below 150ppm. The Al₂O₃ dopant is first coated with 0.08 wt. % of fumed silicaprior to being mixed into the batch of SiO₂. The composition is thenfused in a high induction furnace at 2000° C., forming quartz tubings(labeled as LSPG 1 in subsequent examples).

Example 2

A UV-blocking glass composition is made with 96 wt. % high puritysilicon dioxide, 4 wt. % Al₂O₃, 200 ppm of titanium, and 500 ppm ofCeO₂, with other impurities kept at below 150 ppm. The Al₂O₃, titanium,CeO₂ dopant mixture is first coated with 0.05 wt. % of fumed silicaprior to being mixed into the batch of SiO₂. The composition is thenfused in a high induction furnace at 2000° C., forming quartz tubings(labeled as LSPG 2 in subsequent examples).

Example 3

Random samples from sections of fused quartz tubings made from thequartz glass composition LSPG1 of Example 1 were measured for OHconcentration (in ppm). Random samples were also obtained fromcommercially available fused quartz glass tubings sold as Vycor® 7907,Vycor® 7913, and Vycor® 7921 from Corning Incorporated of Corning, N.Y.and measured for OH concentration. Standard deviations were measured andthe results are as follows in Table 1:

TABLE 1 Example 1 Vycor 7907 Vycor 7913 Vycor 7921 Tubing Tubing TubingTubing 39.15 241.56 124.46 118.83 39.82 277.49 153.54 123.66 36.66267.46 110.11 105.43 36.09 267.21 130.27 89.35 36.14 251.51 116.89119.28 36.21 268.57 212.04 122.62 224.87 224.38 210.58 91.48 83.6 77.0766.99 90.45 Ave. OH 37.345 262.300 136.909 113.195 Stand. Dev. 1.68313.171 57.905 13.387

Example 4

Lamp envelopes were made out of randomly selected fused quartz tubingsmade from the composition LSPG 1 of Example 1 and the Vycor® 7913tubings. No adjustments were made to the lamp manufacturing line toaccount for the differences in the physical and chemical properties ofthe tubings. FIG. 2 is a photograph comparing the lamps made from thequartz composition of the invention (two lamps on the right hand side)and lamps made from the composition of the prior art (two lamps on theleft side of the picture), showing deformity in the two lamps made froma composition of the prior art

Example 5

UV transmittance data between 200 to 400 nm were measured for samples ofquartz tubings made from: a) compositions LSPG1 and LSPG2 of Examples1-2; b) commercially available GE214 natural quartz from GE Quartz, Inc.of Ohio, FIG. 3 is a graph comparing the UV transmission data, showingthat the quartz glass products of the invention as made from the samebatch have a much narrower UV transmission variation band compared to aquartz glass composition of the prior art (GE214 quartz).

Also as illustrated, the quart glass products of the invention absorb atleast 90% of UV radiation between 250 to 400 nm, and at least 87% of theUV radiation between 200 to 400 nm. Although not measured/illustrated inFIG. 3, it is noted that publicly available transmission data for Vycor7913 shows a significant jump from <5% to about 90% from 200 to 300 nmfor Vycor 7913, as compared to a narrow variation of less than 10% forthe compositions of the invention in the range of 200 to 300 nm.

Example 6

UV transmittance data between 200 to 800 nm were measured for samples ofquartz tubings made from composition LSPG2 of Example 2 and commerciallyavailable products including Osram 406, Philips 521, and Vycor 7907.FIG. 4 is a graph comparing the UV transmission data for the varioussamples. As noted, the transmission data for the sample of the inventionshows little variation in the 200-300 nm range compared to the samplesof the prior art.

Example 7

OH concentrations were measured for samples of quartz tubings made fromcomposition LSPG2 of Example 2 and commercially available productsincluding Osram 406, Philips 521, Vycor 7907, and Philips low viscosityglass. FIG. 5 is a graph comparing the OH concentration in ppm for thecomposition Example 2 vs. the various prior art glass samples(commercially available glasses indicated as reference samples 1-5). Asshown in the Figure, the sample of the invention has a much loweraverage OH level and standard deviation compared to the samples of theprior art.

Example 8

Glass pucks having dimensions of 4″ by 4″ by 1″ (in thickness) are fusedfrom: (1) comparative glass composition containing 96 wt. % high puritysilicon dioxide, 4 wt. % Al₂O₃ as a dopant, and with other impuritieskept at below 150 ppm; and (2) a composition of the invention, LSPG1composition of Example 1 with 0.08 wt. % of fumed silica. FIG. 6 is aphotograph comparing the two glass pucks side by side, comparative glasspuck on the left of the picture and the LSPG1 glass puck on the right.As shown, the glass on the right has a greater degree of clarity (ortransmission through the glass) compared to the glass on the left, withthe letters underneath the LSPG1 puck on the right appear to be moreclear/easier to read.

Examples 9-13

Various samples of doped fused quartz glass were produced and theirrespective viscosity versus temperature performance was recorded. Theexamples were fused according to the previously described procedure, andthe viscosity (in poise) was measured as a function of temperature. Theresults are set forth in FIG. 7, which shows the log viscosity versustemperature. From this data, the softening temperature (temperature atwhich the glass has a viscosity of 10^(7.6) poise) of each sample wascalculated. The results are set forth below in Table 2.

TABLE 2 Softening Ex. Sample ID Compositions Temperature 9 LSPG 3 SiO₂doped with 0.845 wt. % Al₂O₃ 1558° C. 10 LSPG 4 SiO₂ doped with 1.685wt. % Al₂O₃ 1535° C. 11 LSPG 5 (ID SiO₂ doped with 3.65 wt. % Al₂O₃1470° C. 207) 12 LSPG 6 SiO₂ doped with 4.986 wt. % Al₂O₃ 1419° C. 13LSPG 7 (ID SiO₂ doped with 3.2 wt. % Al₂O₃, 1454° C. 247 on 0.18 wt. %CeO₂, 0.03 wt. % TiO₂ chart)

As can be seen, all of these samples exhibited a softening temperaturethat was dependent upon the dopant content, and many are lower than thatof pure fused quartz glass which can range from 1500-1680° C. Therefore,it can be seen that increasing the dopant content in the glass (in theseexamples aluminum oxide) resulted in a reduction in the temperaturerequired to achieve a particular viscosity. Furthermore, increasing thealuminum oxide content in the glass results in reduced viscosity at aparticular temperature.

Extraction Testing:

The composition of Example 13 (LSPG7) was then selected for extractiontesting to compare the amount of extractables leached from the glasscompared to the amount extracted from pure quartz glass as well astraditional pharmaceutical grade borosilicate glass and soda-lime glasscontainers. The containers had the following compositions anddimensions:

214A: Momentive 214 A tube ID 10×OD13-80 mm, pure fused quartz glass(available from Momentive Performance Materials Quartz Inc.) LSPG7: LAHFD70000496 IV, 11.7×14.1×200 mm, BULKAG03 (SiO₂ glass doped with 3.2 wt.% Al₂O₃, 0.18 wt. % CeO₂, 0.03 wt. % TiO₂)

BSi Schott: Type 1 glass, pharmaceutical grade borosilicate glass vial:(Outer Diameter 24 mm and height: 45 mm). Typical chemical compositionby wt %: SiO₂ (75%), B₂O₃ (10.5%). Al₂O₃ (5%), CaO (1.5%), BaO (<1%),Na₂O (7%) (from Schott).

BSi SD: Neutral Borosilicate Glass: Vials (Inner Diameter 22 mm andOuter Diameter 24 mm). Typical chemical composition by wt %: SiO₂ (76%),Al₂O₃ (2.5%), RO (0.5%), R₂O (8%) and B₂O₃ (12%). (From ShangdongPharmaceutical Glass Co. Ltd.)

Na—Ca SD: Soda lime silicate glass: Vials (10 ml and 20 ml). Typicalchemical composition by wt %: SiO₂ (71%), Al₂O₃ (3%), RO (12%) and R₂O(15%) (From Shangdong Pharmaceutical Glass Co. Ltd.)

Sample Preparing and Testing:

First, the tubes or vials were crushed into 5-10 mm size pieces using azirconia hammer. Approximately 100 g of each sample was then washed inDI water three times. After that, the crushed samples were washed with5% HF followed by a DI water rinse. After the washed crushed sampleswere dried, a nylon screen mesh and zirconia mortar and pestle was usedto further crush the samples into cullet with particles approximately300 to 420 micrometers in size. Then AR grade alcohol was used to washthe cullet samples and the samples were then dried in quartz glassbeaker. Then, 10.0 g of each sample was subjected to HCl digestion byhydrothermally treating a 10.0 g of a sample with 50 ml 0.4M HClsolution in a Parr teflon digestion bomb at 121° C. for 2 hours. Aftercooling, 40 ml of the resultant residual solution from each sample wastested for various leachants by ICP-AES testing. The results are shownin Table 3.

TABLE 3 Element Leached Content In Residual Leaching Solution Element214 A LSPG7 BSi Schott BSi SD Na-Ca SD mg/L (ppm) Mean STDEV Mean STDEVMean STDEV Mean STDEV Mean STDEV Na 0.018 0.001 0.057 0.002 7.883 0.0018.740 0.473 42.341 7.948 Ca 0.029 0.009 0.032 0.005 1.002 0.104 0.9560.067 2.647 0.030 B <0.01 <0.01 2.710 0.319 3.322 0.167 0.102 0.011 Al0.022 0.007 0.021 0.029 1.419 0.023 1.596 0.124 0.452 0.102 Ba <0.001<0.001 0.003 0.000 0.028 0.002 0.003 0.002 Fe 0.022 0.001 0.027 0.0010.016 0.001 0.013 0.002 0.018 0.004 K 0.007 0.001 0.008 0.001 0.0360.003 0.036 0.002 0.128 0.019 Mg 0.004 0.001 0.005 0.001 0.013 0.0010.006 0.001 0.777 0.166 As <0.02 <0.02 0.021 0.002 0.029 0.000 0.1220.022 Cd <0.001 <0.001 <0.001 <0.001 <0.001 Cr <0.008 <0.008 <0.008<0.008 <0.008 Pb <0.009 <0.009 <0.009 <0.009 <0.009 Sb <0.01 <0.01 <0.01<0.01 <0.01

U.S. Pat. No. 6,537,626 indicated cationic extraction data for Type 1 isSchott borosilicate glass vials and Type 1 plus is comprised of vialswhere the interior surface had been coated with silica to minimize thecationic extraction. Type 1 Shott borosilicate glass vials exhibitrelative high cationic extraction (Na (3.5 ppm), Ca (1.1 ppm), B (3.5ppm) and Al (2.3 ppm)). Due to the pure silica coating, Type 1 pluspharmaceutical containers exhibit extremely low cationic extraction(below the detection limit of the equipment used: Na (<0.01 ppm), Ca(<0.05 ppm), B (<0.1 ppm) and Al (<0.05 ppm)). The current invention,however, provides an alternative to coated borosilicate glasses (Type 1plus) glasses, in that it provides monolithic, homogeneous, high purityfused quartz glass and lower softening point, high silica glasses basedupon doping with non-traditional modifiers that minimize cationicextraction when said containers come into contact with an aqueous drugformulation. This reduces the manufacturing complexity and high cost ofthe CVD-based silica coating used to manufacture Type 1 plus containers.Type 1 plus containers must first be formed by thermal processing, suchas flame conversion, of a tube of borosilicate glass into apharmaceutical container (eg, vial, syringe, cartridge, etc). Thatcontainer is then CVD coated with a layer of silica to mask theinherently poor chemical durability of the underlying borosilicate glassand/or even lower durability regions that were formed during thermalprocessing (eg., from the volatilization and redeposition of alkalioxide, alkaline earth oxide, and/or borate rich phases during thermalprocessing). Therefore Type 1 plus containers are both encumbered bymulti-step processing (thermal processing and then CVD coating) and theyare not a monolithic/homogeneous glass solution, rather they arecomprised of a masking layer that may have inherent long term durabilityproblems when used for the long term storage of drugs (especially liquidbased drugs) in a pharmaceutical package (such as a vial, syringe,cartridge, etc).

Results:

The fused quartz glass sample (214A in above table) exhibited As, Cd,Cr, Pb and Sb leaching that was below detectable limits. Likewise, theAs, Cd, Cr, Pb and Sb leached by the LSPG5 sample (SiO₂ glass doped with3.2 wt. % Al₂O₃, 0.18 wt. % CeO₂, 0.03 wt. % TiO₂ as prepared above)were all below detectable limits. In contrast, the BSi SD and BSi Schottglasses, which are commonly used within the pharmaceutical packagingindustry, exhibited approximately 0.2 mg/L of As (a toxic element thatcould potentially poison a pharmaceutical formulation).

The 214A and LSPG7 samples both exhibited B leaching that was below thedetection limit, and at least 270 times less than that leached from theBSi Schott or the BSi SD borosilicate glasses. Finally, the LSPG7 and214A samples were very resistant to Na, Ca, Al, K, and Mg leaching,while the BSi Schott, BSi SD and Na—Ca SD glasses exhibited much higherleaching of these elements as shown in the Table 3.

According to standard testing methods, LSPG7 also exhibits excellentproperties with respect to Hydrolytic resistance (ISO 719)/YBB00362004at 98° C. and YBB00252003 at 121° C. (Results: 0.00 mL hydrochloricsolution/g cullet); Acid resistance (DIN 12116)/YBB00342004 (Results:0.2 mg/dm²); Alkali resistance (ISO 695)/YBB00352004 (Results: 49mg/dm²).

The 214A and LSPG glasses exhibit exceptionally low cationic leaching,which is expected to be similar to that from a SiO₂ coated glasscontainer (e.g., a Type 1 plus Schott container). However, fromproduction cost and quality control perspectives, containers producedfrom the glass described herein (a monolithic, homogeneous modifiedsilica glass tubing with low working point temperature) would have anadvantage compared with Type I plus technology in that the containerswould be made from homogeneous low extractable glass having anappropriate working point temperature to enable direct flame conversionprocessing of tubing into pharmaceutical packages without the need forcoating. In contrast, Type I plus containers have a silica coating thatis used to “mask” the cation leaching from the homogeneous, baseborosilicate glass that was used to fabricate the pharmaceuticalpackage. The coating process is expensive and cumbersome (requiring aseparate manufacturing line/process that is used to apply the silicacoating to the interior of the container after thermal conversionprocess), and may not be applicable to all complex shapes/formats,especially some of the complex formats required for prefilledinjectables, pens and/or other complex drug delivery packages.Furthermore, the thermal process to convert the BSi glass to a containermay cause volatilization of alkali oxide, alkaline earth oxide, and/orborate in the glass composition followed by their re-deposition onsurface of the container. Hence, the surface of the containers mayalready be heterogeneous before coating, which can result in loss ofdurability and integrity of the Type 1 plus article.

The foregoing description identifies various, non-limiting embodimentsof glass compositions and articles made therefrom in accordance withaspects of the present invention. Modifications may occur to thoseskilled in the art and to those who may make and use the invention. Thedisclosed embodiments are merely for illustrative purposes and notintended to limit the scope of the invention or the subject matter setforth in the following claims.

1. A silica glass composition comprising about 92 to about 99.9 wt. %SiO₂ and about 0.1 to about 8 wt. % of a dopant selected from Al₂O₃,GeO₂, Ga₂O₃, CeO₂, ZrO₂, TiO₂, Y₂O₃, a rare earth oxide, or mixtures oftwo or more thereof, wherein the composition does not contain anappreciable amount of alkali metals, alkaline earth metals, or borateions.
 2. The glass composition of claim 1, wherein a fused glass articleformed from the composition has a total extractable metal concentrationof about 8 mg/L or less when subjected to HCl digestion, the totalextractable metal concentration being represented by the totalconcentration of Al, B, Na, Ca, K, Li, Ba, and Mg extracted upon HCldigestion.
 3. The glass composition of claim 1 comprising about 96 toabout 99.9 wt % SiO₂.
 4. The glass composition of claim 2, wherein thetotal extractable metal concentration is about 5 mg/L or less.
 5. Theglass composition of claim 2, wherein the total extractable metalconcentration is about 1 mg/L or less.
 6. The glass composition of claim1, wherein the glass composition exhibits a working point temperature inthe range of from about 1,000 to about 2,000° C.
 7. The glasscomposition of claim 1, wherein the glass composition exhibits asoftening point temperature in the range of about 500 to about 1,700° C.8. The glass composition of claim 1, wherein a fused glass articleformed from the glass composition exhibits the following leachingcharacteristics when subjected to HCl digestion: Na (<7.0 mg/L), Ca(<1.0 mg/L), B (<2.5 mg/L), Al (<1.25 mg/L), K (<0.03 mg/L), or Mg(<0.01 mg/L).
 9. The glass composition of claim 1, wherein a fused glassarticle formed from the glass composition exhibits the followingleaching characteristics when subjected to HCl digestion: Na (<7.0mg/L), Ca (<1.0 mg/L), B (<2.5 mg/L), Al (<1.25 mg/L), K (<0.03 mg/L),and Mg (<0.01 mg/L).
 10. The glass composition of claim 1, wherein afused glass article formed from the glass composition exhibits thefollowing leaching characteristics when subjected to HCl digestion: Na(<0.1 mg/L), Ca (<0.05 mg/L), B (<0.01 mg/L), Al (<0.05 mg/L), Mg (<0.01mg/L), or K (<0.01 mg/L).
 11. The glass composition of claim 1, whereina fused glass article formed from the glass composition exhibits thefollowing leaching characteristics when subjected to HCl digestion: Na(<0.1 mg/L), Ca (<0.05 mg/L), B (<0.01 mg/L), Al (<0.05 mg/L), Mg (<0.01mg/L), and K (<0.01 mg/L).
 12. The glass composition of claim 1, whereinthe total concentration of metal impurities is about 1.0 wt. % or less.13. The glass composition of claim 1, wherein the total concentration ofmetal impurities is about 0.5 wt. % or less.
 14. The glass compositionof claim 1, wherein the total concentration of metal impurities is about0.015 wt. % or less.
 15. The glass composition of claim 1, furthercomprising a UV blocker comprising Ti, Ce, Fe, or combinations of two ormore thereof, the UV blocker being present in amount of from about 0.001to about 0.5 wt %.
 16. The glass composition of claim 1, wherein a fusedglass article formed from the glass composition has an OH concentrationof 0.5% or less, a Cl concentration of 0.5% or less, or an OHconcentration and Cl concentration of 0.5% or less.
 17. The glasscomposition of claim 1, wherein a fused glass article formed from theglass composition has an OH concentration of 150 ppm or less, a Clconcentration 150 ppm or less, or an OH concentration and Clconcentration of 150 ppm or less.
 18. The glass composition of claim 1,wherein a fused glass article formed from the glass composition has anOH concentration of 50 ppm or less, a Cl concentration of 50 ppm orless, or an OH concentration and Cl concentration of 50 ppm or less. 19.The glass composition of claim 1, wherein a fused glass article formedfrom the glass composition has an OH concentration of 10 ppm or less, aCl concentration of 10 ppm or less, or an OH concentration and Clconcentration of 10 ppm or less.
 20. The glass composition of claim 1,wherein the glass composition exhibits a coefficient of thermalexpansion of less than 3 ppm/K.
 21. The glass composition of claim 1,wherein the glass composition exhibits a coefficient of thermalexpansion less than 2 ppm/K.
 22. The glass composition of claim 1,wherein the glass composition exhibits a coefficient of thermalexpansion of less than 1 ppm/K.
 23. The glass composition of claim 1,having a working point temperature of about 1,700° C. or less.
 24. Aglass article comprising a silica glass composition comprising about 92to about 99.9 wt. % SiO₂ and about 0.1 to about 8 wt. % of a dopantselected from Al₂O₃, GeO₂, Ga₂O₃, CeO₂, ZrO₂, TiO₂, Y₂O₃, a rare earthoxide, or mixtures of two or more thereof, wherein the silica glasscomposition does not contain an appreciable amount of alkali metals,alkaline earth metals, or borate ions, the article having a totalextractable metal concentration of about 8 mg/L or less when subjectedto HCl digestion, the total extractable metal concentration beingrepresented by the total concentration of Al, B, Na, Ca, K, Li, Ba, andMg extracted upon HCl digestion; wherein the glass article is formed bya continuous draw process.
 25. A silica glass composition comprising atleast 99.9% wt. % SiO₂ and a dopant selected from Al₂O₃, GeO₂, Ga₂O₃,CeO₂, ZrO₂, TiO₂, Y₂O₃, a rare earth oxide, or mixtures of two or morethereof in an amount of about 0.1 to about 0.0001 wt. %, wherein thecomposition does not contain an appreciable amount of alkali metals,alkaline earth metals, or borate ions.
 26. The glass composition ofclaim 25 comprising greater than about 99.95 wt. % SiO₂.